Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

e-Posters

13P - Incidental germline findings from tumor molecular profiling for precision oncology: is it common and how to manage?

Date

06 Oct 2021

Session

e-Posters

Presenters

Maxim Ivanov

Citation

Annals of Oncology (2021) 32 (suppl_6): S1345-S1371. 10.1016/annonc/annonc740

Authors

M. Ivanov1, A. Lebedeva2, D. Seriak3, E. Rozhavskaya4, M. Sharova4, D. Vardhan5, A. Baranova5, J. Shaykhutdinova4, V. Mileyko4

Author affiliations

  • 1 Moscow Institute of Physics and Technology, Dolgoprudny/RU
  • 2 Lomonosov Moscow State University, 119991 - Moscow/RU
  • 3 First Moscow State Medical University named after I.M. Sechenov (Sechenov Universaty), 119991 - Moscow/RU
  • 4 Atlas Oncodiagnostics, LLS, 121069 - Moscow/RU
  • 5 George Mason university, 22030 - Fairfax/US
More

Abstract 13P

Background

A fraction of patients referred for tumor-only complex molecular profiling may harbor germline variants in genes associated with the development of hereditary cancer syndromes (HCS). Bioinformatic management and reporting of such incidental germline findings are not standardized.

Methods

Data from NGS sequencing of tumor-only samples from patients referred for complex molecular profiling were analyzed in order to identify germline variants in HCS-associated genes. Analysis of variant origin was performed employing bioinformatic algorithms followed by manual curation. If possible, variant origin was validated by Sanger sequencing using patients’ normal tissue. Variants’ pathogenicity was assessed according to ACMG/AMP.

Results

NGS data from 183 patients (75 men [41.0%]; mean [SD] age, 57.7 [13.3] years) were obtained. The most common tumor types were colorectal (19%), pancreatic (13%), and lung cancer (10%). We detected 56 sequencing variants (40 patients) in genes associated with HCS. Of them, 17 (14 patients) were predicted to be of germline origin with 6 variants interpreted as pathogenic (PV) or likely pathogenic (LPV) and 9 as variants of uncertain significance (VUS). Bioinformatics prediction of variant origin was concordant with manual curation for the 41 (97%) missense variants in HCS associated genes. Based on the results of our study we estimate that Sanger sequencing using a patient's normal tissue would be required in ∼1-7% of cases (PV or LPV found in HCS genes) while referring for genetic counseling in ∼2-15% of cases (PV, LPV or VUS found in HCS genes).

Conclusions

Incidental findings of pathogenic germline variants are common in data from cancer patients referred for complex molecular profiling. We propose an algorithm for the management of variants in genes associated with HCS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Rozhavskaya, M. Sharova, J. Shaykhutdinova, V. Mileyko: Financial Interests, Personal, Affiliate: Atlas Oncology Diagnostics. A. Baranova: Financial Interests, Institutional, Advisory Board: Atlas Oncology Diagnostics. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.